Compelling evidence links dietary sodium intake with the prevalence of hypertension in several human population groups. Epidemiologic studies of man and selective inbreeding studies in rats suggest that most population groups contain individuals who are either sodium-sensitive, sodium-resistant, or who lie somewhere in between. Our preliminary short-term studies suggest that the hemodynamic basis of these differences lies in the ability of sodium-resistant subjects to decrease vascular resistance when cardiac index rises during a high sodium diet, while sodium-sensitive subjects fail to lower resistance adequately. Additional studies are needed to verify this important point and to determine its long-term significance. Non-invasive methods for estimating changes in vascular resistance in response to dietary sodium manipulation using echo-cardiography and venous occlusion plethysmography will be tested as a means to identify sodium-sensitive individuals in the population who might benefit from preventive dietary measures. Studies are described in eight areas: 1. To determine whether the response to short term sodium depletion and repletion seems to identify individuals who will become hypertensive if they chronically ingest the amount of sodium found in the usual North American diet and to clariy the mechanisms by which sodium-resistant individuals adept to a high sodium intake. 2. To test the possibility that dietary potassium supplementation will blunt the hypertensive effect of sodium. 3. To determine if attenuation of the microvasculature is a characteristic that identifies sodium-sensitive individuals. 4. To determine if dietary magnesium of calcium intake alters blood pressure or the response to dietary sodium by an effect on vascular reactivity or the microcirculation. 5. To investigate abnormal erythrocyte sodium-potassium cotransport as a predictor of sodium-sensitivity. 6. To study the relationship of circulating inhibitors of Na+, K+, ATPase with arterial blood pressure, vascular resistance and the response to sodium. 7. To test the hypothesis that abnormalities of left ventricular diastolic function precede the development of elevated blood pressure and serve to identify potentially hypertensive individuals. 8. To study the relationship of urinary N-acetyl-B-Glucosaminidase to sodium sensitivity and the eventual development of hypertension.